Ru-Catalyzed Regioselective Cascade Annulation of Acrylamides with 2-Alkynoates for the Synthesis of Various 6-Oxo Nicotinic Acid Esters

Abstract

Ru-catalyzed regioselective cascade annulation of acrylamides with 2-alkynoates via aza-Michael/C−H activation sequence for the synthesis of various 6-oxo nicotinic acid esters is described. The regioselectivity of the protocol has been confirmed by performing silver mediated protodecarboxylation of the corresponding 6-oxo nicotinic acid to furnish 2-pyridone. The developed protocol is copper or silver salt-free and uses inexpensive, safe, and environmentally benign peroxide-based "oxone" as the sole oxidant. A redox-neutral version of the protocol is also demonstrated.

20 Years of Forging N-Heterocycles from Acrylamides through Domino/Cascade Reactions

“…Recently, Mhaske et al presented a ruthenium catalyzed annulation of acrylamides 1s with 2-alkynoates to produce 6oxo-nicotinic acid esters 89m (Scheme 34, c). 109 The system consisted in acrylamides (1 equiv.) and the alkynoates (2 equiv.)…”

“…Recently, Mhaske and Garad presented a rutheniumcatalyzed annulation of acrylamides 1s with 2-alkynoates to produce 6-oxo-nicotinic acid esters 89m (Scheme 34, c). 109 The reaction system consisted of acrylamide (1 equiv) and the alkynoate (2 equiv) mixed with the ruthenium dimer [RuCl 2 (p-cymene)] 2 (5 mol%) as the catalyst, KOAc (10 mol%) as the basic additive and Oxone as the terminal oxidant. Under these conditions, 2-pyridones 89m were obtained in moderate yields (20 examples).…”

Manganese(I)‐Catalyzed Site‐Selective C6‐Alkenylation of 2‐Pyridones Using Alkynes via C−H Activation

“…[8] As such, ever-growing research atten-tion has been focused on the development of efficient protocols for the synthesis of functionalized 2pyridones. [9] While traditional cross-coupling reactions of halogenated 2-pyridones are still widely employed to access functionalized 2-pyridone derivatives, [10] direct functionalization of 2-pyridone CÀ H bonds using transition-metal catalysts has recently evolved as an efficient and versatile synthetic tool for producing such products in a highly step-and atom-economical manner with promising results being achieved in regioselective functionalization of 2-pyridones at the positions of C3, C4, C5 and C6. [11] In particular, since the seminal work by Hirano and Miura on the introduction of a pyridine group on the nitrogen atom of the 2-pyridone skeleton to promote C6-selective heteroarylation of 2-pyridones, [12a] chelation-assisted direct alkylation, [12b,i,j,m,o,s,t] arylation, [12f,h,k] borylation, [12e] thiolation, [12g] annulation, [12c,d,l,n] and amidation [12p-r] of 2-pyridones at the C6 positions using transition-metal catalysts have been successfully realized, mainly involving rhodium and ruthenium complexes.…”

Dichalcogenides/Oxone®‐Mediated Cyclization of (Z)‐Chalcogenoenynes under Ultrasound Irradiation

“…In this sense, Oxone ® is an easy to handle oxidant agent, stable under several conditions and that presents a safe manipulation and disposal, due to its low toxicity. Oxone ® (2KHSO 5 ⋅KHSO 4 ⋅K 2 SO 4 ) acts as oxidant in many selective oxidation reactions [16] and it has been used to synthesize several heterocyclic compounds by intra- [17][18][19][20][21][22][23][24] and intermolecu-lar reactions, [25][26][27][28][29] including oxidative cyclization ones. [30][31][32][33][34][35][36] Recently, our group has explored the application of this oxidant in the synthesis of organoselenium and organotellurium compounds, [37][38][39][40][41][42] such as 2,3-bis-organochalcogenyl-benzo [b] chalcogenophenes, via the electrophilic cyclization of 2functionalized selanyl-and sulfanylalkynes (Scheme 1a).…”